Studies on role of calmodulin in Ca2+ regulation of rabbit ileal Na and Cl transport
Donowitz, M.; Wicks, J.; Madara, J.L.; Sharp, G.W.
American Journal of Physiology 248(6 Pt 1): G726-G740
1985
ISSN/ISBN: 0002-9513 PMID: 2408486 Document Number: 248625
To study the role of calmodulin in regulation of rabbit ileal active electrolyte transport by calcium2+, the effects of the Ca2+-calmodulin antagonist naphthalenesulphonamides W12 and W13 and the weak Ca2+-calmodulin antagonist promethazine, a phenothiazine, were studied on basal ileal sodium and chloride transport and on secretion stimulated by Ca2+ and by cAMP. The naphthalenesulphonamides and promethazine all stimulated basal ileal Na and Cl absorption. The stimulation of Na absorption was dependent on Cl in the bathing solutions, and the stimulation of Cl absorption was Na-dependent. This suggests that the transport process stimulated was the neutral, linked NaCl absorptive process. W13, which is a better Ca2+-calmodulin antagonist but has similar hydrophobic properties to W12, stimulated active ileal absorption at a lower concentration than W12, suggesting that the naphthalenesulphonamide-induced stimulation of active ileal absorption was not due to the hydrophobic properties of these drugs but could be due to their effects on the Ca-binding protein calmodulin. W12, W13 and promethazine did not change paracellular transport, not affecting dilution potentials or structural features of the paracellular pathway. W12 and W13 did not decrease the changes in active ileal Na and Cl transport caused by increasing ileal cAMP content or intracellular Ca2+. This suggests that calmodulin is not directly involved in the active electrolyte secretion caused by increased intestinal Ca2+ or cAMP.